Induction of apoptosis and cell growth inhibition by protein 4.33

Abstract

There is disclosed an isolated cDNA sequence (SEQ ID NO:1) encoding a P4.33 polypeptide and comprising a coding region (SEQ ID NO:2) of the sequence described in SEQ ID NO:1, or a sequence having at least 90% homology with the coding region of SEQ ID NO:1. The P4.33 polypeptide functions as a specific cell-surface receptor for IGFBP-3, and undergoes nuclear translocation in combination with IGFBP-3. In particular aspects, IGFBP-3 and P4.33 (IGFBP-3R) cooperatively suppress DNA synthesis and cell growth, and induce caspase activation and apoptosis in cancer cells, indicating that P4.33 is an important mediator of IGF-independent growth inhibitory actions of IGFBP-3. The P4.33:IGFBP-3 system of the present invention can be used, inter alia, in screening and diagnostic assays, and for therapeutic methods for cancer treatment and tumor suppression.

1 .- 54 . (canceled) 
     
     
         55 . An isolated nucleic acid encoding a polypeptide comprising SEQ ID NO:2 or an IGFBP-3 binding portion thereof. 
     
     
         56 . The isolated nucleic acid of  claim 55 , comprising SEQ ID NO:1 or a sequence having at least 90% sequence identity with the coding region of SEQ ID NO:1 or with an IGFBP-3 binding portion thereof. 
     
     
         57 . An expression vector having a DNA sequence that codes on expression for a polypeptide comprising SEQ ID NO:2 or an IGFBP-3 binding portion thereof. 
     
     
         58 . The expression vector of  claim 57 , comprising SEQ ID NO:1 or a sequence having at least 90% sequence identity with the coding region thereof. 
     
     
         59 . The expression vector of  claim 57 , comprising a viral expression vector. 
     
     
         60 . The expression vector of  claim 59 , comprising an adenovirus or adeno-associated virus expression vector. 
     
     
         61 . An isolated polypeptide comprising SEQ ID NO:2 or an IGFBP-3 binding portion thereof. 
     
     
         62 . The isolated polypeptide of  claim 61 , comprising a heterologous polypeptide fused to SEQ ID NO:2 or to an IGFBP-3 binding portion thereof. 
     
     
         63 . The isolated polypeptide of  claim 61 , consisting of SEQ ID NO:2 or an IGFBP-3 binding portion thereof. 
     
     
         64 . A transfected or recombinant cell comprising an expression vector encoding a polypeptide comprising SEQ ID NO:2 or an IGFBP-3 binding portion thereof. 
     
     
         65 . The transfected or recombinant cell of  claim 64 , comprising and expression vector comprising SEQ ID NO:1 or a sequence having at least 90% sequence identity with the coding region thereof. 
     
     
         66 . An antibody, or antigen-binding portion thereof, specific for SEQ ID NO:2.